Fluoxetine, a common antidepressant drug, is widely used for mental disorders therapy in adolescents. Previous animal experiments have indicated that exposure to fluoxetine during adolescence leads to persistent behavioral changes and neuroplasticity in the hippocampal formation and cortex which may continue until adulthood. Therefore, in the present experimental study, we examined the effects of chronic fluoxetine exposure (5 mg/kg/day, gavage) throughout adolescence (postnatal day 21–60) on passive avoidance learning and memory, pain sensitivity, and brain-derived neurotrophic factor (BDNF) level in the prefrontal cortex of young adult male and female rats. Passive avoidance learning, memory, and nociception were assessed by the shuttle box and hot plate tests respectively. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was applied to estimate the BDNF mRNA expression. Our data showed that chronic administration of fluoxetine had an increasing effect on passive avoidance memory in female animals. As well as, chronic fluoxetine treatment decreased latency of response to thermal stimulus in male and female rats. The mRNA expression of BDNF in the prefrontal cortex significantly increased in fluoxetine- exposed female rats.

In conclusion, chronic fluoxetine treatment has sex-dependent effects on passive avoidance memory and BDNF mRNA expression, but the pain threshold decreases in both sexes. Therefore, passive avoidance memory, pain sensitivity, and the BDNF level are influenced by the manipulation of the serotonergic system.

氟西汀是一种常见的抗抑郁药，广泛用于青少年精神障碍的治疗。先前的动物实验表明，在青春期接触氟西汀会导致海马结构和皮层的持续行为变化和神经可塑性，这种变化可能会持续到成年。因此，在本实验研究中，我们检查了整个青春期（出生后第 21-60 天）长期接触氟西汀（5 毫克/公斤/天，灌胃）对被动回避学习和记忆、疼痛敏感性和脑源性神经营养的影响。年轻成年雄性和雌性大鼠前额叶皮层中的因子 (BDNF) 水平。被动回避学习、记忆和伤害感受分别通过穿梭箱和热板测试进行评估。应用定量逆转录酶-聚合酶链反应 (RT-PCR) 来估计 BDNF mRNA 表达。我们的数据表明，长期服用氟西汀对雌性动物的被动回避记忆有越来越大的影响。此外，慢性氟西汀治疗降低了雄性和雌性大鼠对热刺激的反应潜伏期。在氟西汀暴露的雌性大鼠中，前额叶皮层中 BDNF 的 mRNA 表达显着增加。

总之，慢性氟西汀治疗对被动回避记忆和BDNF mRNA表达具有性别依赖性影响，但两性的痛阈均降低。因此，被动回避记忆、疼痛敏感性和 BDNF 水平受 5-羟色胺能系统操纵的影响。